Department of Anaesthesiology and Pain Therapy, Inselspital, University Hospital Bern, Freiburgstr., 3010 Bern, Switzerland.
Forensic Sci Int. 2010 Dec 15;203(1-3):63-70. doi: 10.1016/j.forsciint.2010.07.003. Epub 2010 Aug 14.
Response to analgesics, anticancer pharmacotherapy and pharmacotherapy of other cancer related symptoms vary broadly between individuals. Age, disease, comorbidities, concomitant medication, organ function and patients' compliance may partly explain the differences. However, the focus of ongoing research has shifted towards genomic variants of phase I and II drug metabolizing enzymes with one important goal being an individual dose adjustment according to a patient's genotype. Polymorphisms of the cytochrome P 450 2D6 influence the metabolism of many drugs including the analgesics codeine, tramadol, hydrocodone and oxycodone, as well as the metabolism of tricyclic antidepressants and the anticancer drug tamoxifen. Other candidate genes such as (opioid)-receptors, transporters and other molecules important for pharmacotherapy in pain management are discussed. Although pharmacogenetics as a diagnostic tool has the potential to improve patient therapy, study results are often equivocal and limited by small sample sizes and often by their retrospective design. Well designed studies are needed to demonstrate superiority of pharmoacogenetics to conventional dosing regimes.
个体之间对镇痛药、抗癌药物治疗和其他与癌症相关症状的药物治疗的反应差异很大。年龄、疾病、合并症、伴随用药、器官功能和患者的依从性可能部分解释了这些差异。然而，目前研究的重点已经转向了 I 期和 II 期药物代谢酶的基因组变异，其中一个重要目标是根据患者的基因型进行个体化剂量调整。细胞色素 P450 2D6 的多态性影响许多药物的代谢，包括镇痛药可待因、曲马多、氢可酮和羟考酮，以及三环抗抑郁药和抗癌药物他莫昔芬的代谢。还讨论了其他候选基因，如（阿片类）受体、转运体和其他在疼痛管理药物治疗中重要的分子。尽管作为一种诊断工具，药物遗传学有可能改善患者的治疗效果，但研究结果往往存在争议，受到样本量小的限制，而且往往受到回顾性设计的限制。需要进行精心设计的研究来证明药物遗传学优于常规剂量方案。
